1. Technical Field
This invention relates to a bioelectrode system for iontophoretic delivery of medicaments.
2. Background Information
Iontophoretic delivery of medicaments has been found useful in a number of different applications including, for example, delivery of pilocarpine salts as a diagnostic test for cystic fibrosis and delivery of lidocaine hydrochloride to anesthetize a localized area prior to some minor surgical procedure such as wart removal.
Typically, systems for iontophoretic delivery of medicaments use two bioelectrodes, one positive and one negative, each placed in electrical contact with a portion of the skin or a mucosal surface of the body. Also typical is that each bioelectrode contains an electrolyte solution at least one of which contains ionized medicament. An electrical power source, such as a battery, is connected to the electrodes to complete the electrical circuit through the body. The charge of the ionized solution determines bioelectrode polarity such that, when current is supplied, the medicament ions migrate away from the electrode and are thereby delivered through the skin.
Some type of enclosure or other fluid-holding means is typically used to contain the ionized electrolyte or medicament solution such that a mechanism or structure on the enclosure is necessary to permit the introduction of solution thereunto. Such structure has typically included some type of orifice containing a plug into which a hypodermic needle or syringe canula may be inserted to allow delivery of the solution through the orifice into the interior of the enclosure, while preventing the outflow of the solution after it has been introduced into the enclosure. The requirement of such solution receiving mechanism or enclosure increases the cost of the bioelectrode system and gives rise to potential spillage and leakage of solution. Such spillage and leakage can result in an inoperative or defective device.
More recent bioelectrode systems have used hydrophilic polymers to form means for holding the medicament and electrolyte solutions. See, for example, the preformed gel body described in U.S. Pat. No. 4,383,529 issued to Webster, incorporated herein by reference. Although such pre-hydrated gel bodies may prevent leakage and spillage problems, there may still be stability and storage problems. To address these problems, bioelectrodes containing initially "dry," but hydratable, holding means for the medicament and electrolyte solutions have been developed. See, for example, the hydratable layers of hydrogel sheets described in Lloyd et al., U.S. Pat. No. 5,236,412, incorporated herein by reference.
In addition, efforts have been directed to developing bioelectrode systems containing initially dry, but hydratable, solution-holding components wherein the means for hydrating the components is also self-contained. Thus, for example, Haak et al., U.S. Pat. No. 5,288,289 and Gyory et al., published international patent application, WO 93/24177, both of which are incorporated herein by reference, disclose various self-contained means for releasing hydrating liquid from liquid-storage components and thereby hydrating the initially dry solution-holding components.
In certain embodiments of the Haak patent, the hydrating liquid-storage components comprise breakable capsules filled with the desired hydrating liquid which are positioned within a layer of material such that the liquid is isolated from the hydratable solution-holding components. Squeezing or flexing of the hydrating liquid-storage component breaks the capsules and releases the hydrating liquid. The hydrating liquid flows onto the electrical current distribution element and through preformed passageways to the hydratable solution-holding component. Optional wicking material is described to enhance rapid transfer of the liquid across the electrode conductor surface where the liquid can flow through the passageways to the hydratable solution-holding component.
It can be seen that the hydrating rate, the completeness of the fluid transfer, and the fluid distribution pattern is affected by the characteristics and properties of the separate elements which must be in fluid communication, i.e., the interposed electrical current distribution element material, the hydrating liquid-storage component material, the hydratable solution-holding component material, and the optional wicking material. Other variables include the size, shape, and other characteristics of the flow through openings between the hydrating liquid-storage component and the hydratable solution-holding component, the distributional arrangement of the capsules within the hydrating liquid-storage component material, and even whether or not all of the capsules break or whether the encapsulized liquid is completely dispensed from the broken capsules. Moreover, inadvertent squeezing or flexing of the hydrating liquid-storage component could occur during manufacture, shipping, storing or handling of the device. Such an occurrence could break some or all of the hydrating liquid-filled capsules and cause premature hydration of the hydratable solution-holding component. Such premature hydration could result in an unusable or defective device.
Alternatively, the bioelectrode system disclosed in the Haak patent comprises separate components such that the hydrating liquid-storage component is covered by a removable liquid-impermeable sheet such that removal of the sheet exposes the hydrating liquid. The hydrating liquid-storage component is attached to one portion of the system. The hydratable solution-holding component is attached to a separate portion of the system. A user of the system removes the liquid-impermeable sheet to expose the hydrating liquid and then manually assembles the separate portions such that the hydrating fluid contacts, and thereby hydrates, the hydratable solution-holding component. Alternatively, the system portions are not separate from each other but, rather, the portion attached to the hydrating liquid-storage component is positioned adjacent to the portion attached to the hydratable solution-holding component such that a folding over maneuver will cause contact of the hydratable solution-holding component with the exposed hydrating fluid. Yet another embodiment has the hydrating liquid-storage component and the hydratable solution-holding component attached to a first portion of the system while a second portion of the system contains pins for puncturing the hydrating liquid-storage component. In this embodiment, manual alignment and assembly of the first and second portions causes the pins to puncture the hydrating liquid-storage component and thereby release the fluid to hydrate the hydratable solution-holding component.
In the above-described devices, the need to manually assemble the separate system portions inhibits inadvertent hydration of the hydratable solution-holding component. Nevertheless, separate, or foldable, portions are more costly and cumbersome to use than a unitary device. Such devices also depend on proper assembly by the user. Mis-alignment or improper use could result in inefficient hydration.
As with the previously discussed Haak embodiments, the hydrating rate, the completeness of the fluid transfer, and the uniformity of fluid distribution in the above-described devices are also affected by the characteristics and properties of the individual components, i.e., the interposed electrical current distribution element material, the hydratable solution-holding component material, the hydrating liquid-storage component material, and the optional wicking material. The precision of the alignment of the system portions with each other will also be a factor. In addition, specifically for the device featuring puncturing pins to release the hydrating liquid, the variability in size and shape of the resultant torn or punctured openings created within the hydrating liquid-storage component material or between the hydrating liquid-storage component and the hydratable solution-holding component will affect the escape and dispensing of the hydrating liquid.
Approaches disclosed by Gyory et al. include a hydrating liquid-storage component which is separated from a hydratable solution-holding component by a liquid-impermeable sheet. Certain embodiments rely on packaging means to protect from inadvertent release of the hydrating liquid and to cause "automatic" hydration upon removal of the device from the package. The packaging means which effect "automatic" hydration include compression means to rupture or burst the liquid-impermeable sheet; blade means to puncture the liquid-impermeable sheet; and pull-tab means to rip or tear the liquid-impermeable sheet. An alternative embodiment attaches the pull-tab means, for ripping or tearing the liquid-impermeable sheet, to a release liner covering a skin contacting surface of the device. In this embodiment, removal of the release liner prior to placement on the patient "automatically" pulls the pull-tab means to rip or tear the liquid-impermeable sheet and thereby release the hydrating liquid. Like the Haak invention, Gyory also discloses liquid flow control means for directing the flow of hydrating liquid through the breached liquid-impermeable sheet to the hydratable solution-holding component.
It can be seen that, in Gyory's devices, it is the liquid-impermeable sheet separating the hydrating liquid-storage component from the hydratable solution-holding component which is physically ruptured, punctured, or ripped. The material comprising the hydrating liquid-storage component, however, remains intact. After the liquid-impermeable sheet is breached and the hydrating liquid is released, the material which formed the now-depleted hydrating liquid-storage component remains positioned within the device. In the case of a ruptured or punctured sheet, all of the now-breached liquid-impermeable sheet material also remains entirely within the device. In the pull-tab embodiment, some of the sheet material is ripped or torn away and is removed from within the device with the attached pull-tab. Nevertheless, in all cases, a substantial portion of the liquid-impermeable sheet material as well as all of the hydrating liquid-storage component material remains within the device following the hydration process.
The rupturing, puncturing, or tearing of the liquid-impermeable sheet material exposes torn edges and, thus, inner layers, of the liquid-impermeable sheet including, for example, foil edges. The hydrating liquid-storage component material and the breached liquid-impermeable sheet material, including exposed torn inner layer edges, remain within the device. These no-longer needed materials could interfere with electrical current distribution. These materials also contact the now-hydrated solution-holding component such that deleterious communication with the solution is possible. For example, over long-term iontophoresis, i.e. many hours, materials such as exposed foil edges could corrode. Thus, it would be advantageous to be able to remove the materials associated with the hydrating liquid-storage component following the hydration process.
Both Haak and Gyory provide liquid-conveying pathways to distribute the hydrating liquid. Such liquid-conveying pathways, however, necessarily affect the transfer of the hydrating fluid because the rate and amount of fluid transferred is limited by the pathway configuration. It would, however, be advantageous to effect essentially uniform transfer of the hydrating fluid directly onto the surface of the hydratable reservoir element.